Magnesium-Dependent RNA Binding to the PA Endonuclease Domain of the Avian Influenza Polymerase

2014 ◽  
Vol 118 (4) ◽  
pp. 873-889 ◽  
Author(s):  
Shiyan Xiao ◽  
Michael L. Klein ◽  
David N. LeBard ◽  
Benjamin G. Levine ◽  
Haojun Liang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Rna Binding ◽  
Endonuclease Domain ◽  
Influenza Polymerase

Screening Anti-influenza Agents that Target Avian Influenza Polymerase Protein PACfrom Plant Extracts Based on NMR Methods

2011 ◽  
Vol 40 (8) ◽  
pp. 801-803 ◽  
Author(s):  
Lin Li ◽  
Sheng-Hai Chang ◽  
Jun-Feng Xiang ◽  
Qian Li ◽  
Huan-Huan Liang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Plant Extracts ◽  
Nmr Methods ◽  
Influenza Polymerase

scholarly journals Mammalian ANP32A and ANP32B proteins drive alternative avian influenza virus polymerase adaptations

2020 ◽  
Author(s):  
Thomas. P. Peacock ◽  
Carol M. Sheppard ◽  
Ecco Staller ◽  
Rebecca Frise ◽  
Olivia C. Swann ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Experimental Evolution ◽  
Human Cells ◽  
Influenza Viruses ◽  
Avian Viruses ◽  
Evolution Approach ◽  
Influenza Polymerase

AbstractANP32 proteins, which act as influenza polymerase co-factors, vary between birds and mammals. The well-known mammalian adaptation, PB2-E627K, enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbour this adaptation. Here, we show that alternative PB2 adaptations, Q591R and D701N also allow influenza polymerase to use mammalian ANP32 proteins. PB2-E627K strongly favours use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs and horses where ANP32A proteins are more strongly pro-viral. In an experimental evolution approach, passage of avian viruses in human cells drives acquisition of PB2-E627K, but not when ANP32B is ablated. The strong pro-viral support of ANP32B for PB2-E627K maps to the LCAR region of ANP32B.

scholarly journals Alleles A and B of non-structural protein 1 of avian influenza A viruses differentially inhibit beta interferon production in human and mink lung cells

2011 ◽  
Vol 92 (9) ◽  
pp. 2111-2121 ◽  
Author(s):  
Muhammad Munir ◽  
Siamak Zohari ◽  
Giorgi Metreveli ◽  
Claudia Baule ◽  
Sándor Belák ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Rna Binding ◽  
Type I Interferons ◽  
Lung Cells ◽  
Type I ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Promoter Activation ◽  
Influenza A Viruses

Non-structural protein 1 (NS1) counteracts the production of host type I interferons (IFN-α/β) for the efficient replication and pathogenicity of influenza A viruses. Here, we reveal another dimension of the NS1 protein of avian influenza A viruses in suppressing IFN-β production in cultured cell lines. We found that allele A NS1 proteins of H6N8 and H4N6 have a strong capacity to inhibit the activation of IFN-β production, compared with allele B from corresponding subtypes, as measured by IFN stimulatory response element (ISRE) promoter activation, IFN-β mRNA transcription and IFN-β protein expression. Furthermore, the ability to suppress IFN-β promoter activation was mapped to the C-terminal effector domain (ED), while the RNA-binding domain (RBD) alone was unable to suppress IFN-β promoter activation. Chimeric studies indicated that when the RBD of allele A was fused to the ED of allele B, it was a strong inhibitor of IFN-β promoter activity. This shows that well-matched ED and RBD are crucial for the function of the NS1 protein and that the RBD could be one possible cause for this differential IFN-β inhibition. Notably, mutagenesis studies indicated that the F103Y and Y103F substitutions in alleles A and B, respectively, do not influence the ISRE promoter activation. Apart from dsRNA signalling, differences were observed in the expression pattern of NS1 in transfected human and mink lung cells. This study therefore expands the versatile nature of the NS1 protein in inhibiting IFN responses at multiple levels, by demonstrating for the first time that it occurs in a manner dependent on allele type.

Crystal structure of an avian influenza polymerase PAN reveals an endonuclease active site

Nature ◽  
2009 ◽  
Vol 458 (7240) ◽  
pp. 909-913 ◽  
Author(s):  
Puwei Yuan ◽  
Mark Bartlam ◽  
Zhiyong Lou ◽  
Shoudeng Chen ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Avian Influenza ◽  
Active Site ◽  
Influenza Polymerase

scholarly journals Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5658 ◽  
Author(s):  
Olive T. W. Li ◽  
Michael C. W. Chan ◽  
Cynthia S. W. Leung ◽  
Renee W. Y. Chan ◽  
Yi Guan ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Factorial Analysis ◽  
Virus Adaptation ◽  
Full Factorial ◽  
Influenza Polymerase

scholarly journals Molecular Basis of Host-Adaptation Interactions between Influenza Virus Polymerase PB2 Subunit and ANP32A

2020 ◽  
Author(s):  
Aldo Camacho Zarco ◽  
Sissy Kalayil ◽  
Damien Maurin ◽  
Nicola Salvi ◽  
Elise Delaforge ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Mammalian Cells ◽  
Binding Mode ◽  
Polymerase Activity ◽  
Host Adaptation ◽  
Binding Modes ◽  
Intrinsically Disordered ◽  
Species Specific ◽  
Intrinsically Disordered Domain ◽  
Influenza Polymerase

AbstractAvian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Adaptive mutants are localised on the C-terminal (627-NLS) domains of the PB2 subunit. In particular mutation of PB2 residue 627 from E to K in avian polymerase rescues activity in mammalian cells. A host transcription regulator ANP32A, comprising a long C-terminal intrinsically disordered domain (IDD), has also been shown to be responsible for this viral adaptation. Human ANP32A IDD lacks a 33 residue insertion compared to avian ANP32A, a deletion that restricts avian influenza polymerase activity in mammalian cells. We determined conformational descriptions of the highly dynamic complexes between 627E and 627K forms of the 627-NLS domains of PB2 and avian and human ANP32A. The negatively charged intrinsically disordered domain of human ANP32A transiently binds to a basic face of the 627 domain, exploiting multiple binding sites to maximize affinity for 627-NLS. This interaction also implicates residues 590 and 591 that are responsible for human-adaptation of the the 2009 pandemic influenza polymerase. The presence of 627E interrupts the polyvalency of the interaction, an effect that is compensated by extending the interaction surface and exploiting an avian-unique motif in the unfolded domain that interacts with the 627-NLS linker. In both cases the interaction favours the open, dislocated form of the 627-NLS domains. Importantly the two binding modes exploited by human- and avian-adapted PB2 are strongly abrogated in the cross interaction between avian polymerase and human ANP32A, suggesting that this molecular specificity may be related to species adaptation. The observed binding mode is maintained in the context of heterotrimeric influenza polymerase, placing ANP32A in the immediate vicinity of known host-adaptive PB2 mutants. This study provides a molecular framework for understanding the species-specific restriction of influenza polymerase by ANP32A and will inform the identification of new targets for influenza inhibition.

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